Posttraumatic Resuscitation Affects Stent Graft Sizing in Patients with Blunt Thoracic Aortic Injury.

Patients with blunt aortic injury often present to the emergency department in a relatively hypovolemic state. These patients undergo extensive inhospital resuscitation. The effect of posttraumatic resuscitation on aortic diameter has implications for stent graft sizing. The potential utility of repeat aortic imaging after resuscitation remains unclear. A retrospective chart review of all adult patients presenting to a Level I trauma center between the years 2007 and 2013 was performed. Fifty-three patients were identified with a diagnosis of traumatic aortic injury. Of those, 10 had 2 CT scans before aortic repair and were selected as the study population for analysis. After resuscitation, there was a significant increase in aortic diameter both proximal and distal to the aortic injury: proximal aortic diameter increase of 1.97 mm and distal aortic diameter increase of 1.48 mm. This retrospective study shows that after resuscitation, there is a significant increase in proximal and distal aortic diameter. Interval reimaging of the thoracic aorta may be beneficial after adequate stabilization of the patient's other injuries. In certain cases, more appropriate sizing may prevent a device-related complication.

Early outcomes and perioperative risk assessment in elective open thoracoabdominal aortic aneurysm repair: An analysis of national data over a five-year period.

Open surgical repair of thoracoabdominal aortic aneurysms remains associated with significant morbidity and mortality. We sought to analyse multicentre national data on early outcomes of open surgical thoracoabdominal aortic aneurysm repair. Patients who underwent open repair of thoracoabdominal aortic aneurysm from 2005 to 2010 were identified from the National Surgical Quality Improvement Program database. The primary endpoint was mortality at 30 days. Patient demographics, clinical variables, and intraoperative parameters were analysed by univariate and multivariate logistic regression methods to identify risk factors for mortality. Of the 682 elective repairs, 30-day outcomes of elective repairs were: 10.0% mortality, 21.6% surgical complications, 42.2% pulmonary complications, 17.2% renal complications, 12.9% cardiovascular complications, 19.2% septic complications, and 6.6% wound complications. Multivariate logistic regression analysis showed that age, ASA-class IV, dependent functional status prior to surgery, and operation time are independent risk factors for mortality. Our study found a higher rate of mortality nationwide, as compared to several previous single center studies.

Influence of the hostile neck on restenosis after carotid stenting.

BACKGROUND: Carotid artery stenting (CAS) for carotid stenosis is favored over carotid endarterectomy (CEA) in patients with a hostile neck from prior CEA or cervical irradiation (XRT). However, the restenosis rate after CAS in patients with hostile necks is variable in the literature. The objective of this study was to quantify differences in the in-stent restenosis (ISR)/occlusion and reintervention rates after CAS in patients with and without a hostile neck. Here we hypothesize that patients with hostile necks have an increased ISR, and that this increase may add morbidity to these patients. MATERIALS AND METHODS: All patients undergoing CAS from 2007 to 2013 for carotid artery stenosis with follow-up imaging at our institution were queried from our carotid database (n = 236). Patients with hostile necks, including both CAS after prior CEA (n = 65) and prior XRT (n = 37), were compared with patients who underwent CAS for other reasons including both anatomical (n = 46) and medical comorbidities (n = 88). The primary end points were ISR, repeat intervention, and stent occlusion. Secondary end points of the study were stroke/myocardial infarction (MI)/death at 30 days, perioperative cardiovascular accident, transient ischemic attack, MI, groin access complications, hyperperfusion syndrome, and periprocedural hypotension or bradycardia. RESULTS: Despite the hostile neck cohort being younger and having lower incidence of chronic obstructive pulmonary disease, coronary artery disease, and renal insufficiency, they had a greater incidence of ISR (11% vs. 4%; P = .03) and required more reinterventions (8% vs. 2%; P = .04). Stent occlusion and periprocedural morbidity/mortality were not different between groups. CONCLUSIONS: Patients with hostile necks have increased risk of restenosis and need for reinterventions after CAS compared with patients without a hostile neck. However, they do not appear to have higher rates of stent occlusion or per-procedural events.

Carotid duplex criteria for patients with contralateral occlusion.

BACKGROUND: Contralateral occlusion (CLO) occurs in approximately 8% of patients undergoing intervention for carotid artery stenosis. Patients with CLO have increased stroke risk compared with patients without CLO, but standard carotid duplex ultrasonography (CDUS) criteria are not a reliable manner to screen or follow patients with CLO. Because appropriate duplex criteria for these patients are not well understood, this article defines CDUS parameters that accurately predict carotid artery stenosis at our institution. METHODS: Sixty-five patients with ipsilateral carotid stenosis and CLO were identified from our institutional database. Fifteen of sixty-five patients had arteriography, computed tomography angiography, or magnetic resonance angiography within 6 mo of CDUS. We determined accuracy of our laboratory's criteria for determining stenosis category compared with three-dimensional imaging. Receiver operating characteristic curves were used to determine optimal peak systolic velocity (PSV), end diastolic velocity (EDV), and systolic ratio (SR) cutoff values for diagnosing ≥50% stenosis in this pilot cohort. Finally, the revised criteria were prospectively applied to a validation cohort (n = 8) from the same institution. RESULTS: Categorization of stenosis by standard PSV, EDV, and SR criteria saw similar accuracy trends in both pilot (46.7, 53.3, and 66.7%) and validation (25, 25, and 62.5%) cohorts. Receiver operating characteristic curve analysis in the pilot cohort identified optimized PSV, EDV, and SR cutoffs (≥250, ≥90, and ≥2.3 cm/s, respectively) for diagnosing ≥50% stenosis. In the pilot cohort, new PSV criteria increased specificity (60%-100%) with minimal decreased sensitivity (90%-80%), whereas new EDV criteria increased specificity (40%-71.4%) and maintained 100% sensitivity. New SR criteria failed to improve sensitivity or specificity above 80%. Similar trends for the new CDUS velocity criteria were observed in the validation cohort. CONCLUSIONS: Increasingly stringent ultrasound parameters can provide reliable criteria for determining ≥50% carotid stenosis in patients with CLO. Further prospective validation that includes more patients with high-grade ipsilateral stenosis will help identify the role of SR in segregating high-grade versus moderate stenosis in CLO patients.

Activities of daily living is a critical factor in predicting outcome after carotid endarterectomy in asymptomatic patients.

BACKGROUND AND PURPOSE: Ability to perform basic daily activity represented by functional status (FNS) before surgery can be assessed in the clinic for determining health status of the patient. We sought to study the effect of FNS on postoperative outcomes after carotid endarterectomy (CEA) in a national data set. METHODS: National Surgical Quality Improvement Project is a national data set, which includes data from >300 hospitals. Patients who underwent CEA were identified by Current Procedural Terminology code and divided into 3 categories based on FNS: independent, partially dependent, and dependent. Thirty-day postoperative stroke, death, and other postoperative complications were identified as the study end point. We used multivariate logistic regression to estimate odds ratio for outcomes while controlling for sex, race, diabetes mellitus, cardiovascular disease, smoking, and other confounders. RESULTS: Of 19 748 CEAs, 19 348 (97.97%) were functionally independent, 377 (1.99%) were functionally partially dependent, and 23 (0.12%) were functionallydependent. In functionally independent group, there were 196 (1.01%) strokes, 84 (0.43%) deaths, and 1416 (7.17%) other complications, whereas in the functionally partially dependent group, there were 14 (3.71%) strokes, 10 (2.65%) deaths, and 80 (21.22%) other complications. In multivariable risk-adjusted model, using functionally independent as reference, functionally partially dependent was associated with death (odds ratio, 3.3; 95% confidence interval, 1.6-6.8; P<0.001), stroke (odds ratio, 3; 95% confidence interval, 1.7-5.4; P<0.001), and other complications (odds ratio, 2.5; 95% confidence interval, 1.9-3.2; P<0.001). CONCLUSIONS: In this national data set, patient's inability to perform basic activities of independent living is associated with adverse postoperative outcomes after CEA. Hence, FNS should be vigilantly assessed in clinic for risk stratification along with other objective factors for gauging risk of adverse outcomes after CEA.

Latent mycobacterium avium infection causing a mycotic suprarenal aortic aneurysm in a human immunodeficiency virus-positive patient.

Mycobacterium avium complex (MAC) infection occurs in up to 50% of advanced-stage human immunodeficiency 1 (HIV-1) infections when the CD4 counts is <50/mm³. We report the case of a 52-year-old HIV-positive patient who presented with a symptomatic, rapidly growing suprarenal abdominal aortic aneurysm. He had been diagnosed and treated for disseminated MAC infection 3 years earlier. He was treated with antiretroviral medications and had a CD4 count >250 cells/mm³ and an undetectable viral load. Open repair was performed using cryopreserved homograft. Microbiologic cultures from the specimen revealed infection with mycobacterium avium. This is the first case to report a mycotic suprarenal aortic aneurysm caused by an active conversion of a latent MAC infection.

Anatomic characteristics of aortic transection: centerline analysis to facilitate graft selection.

BACKGROUND: Traumatic transection of the thoracic aorta is a life-threatening complication that most commonly occurs after high-speed motor vehicle collisions. Although such injuries were previously treated with open surgical reconstruction, they are now more commonly being treated with endovascularly placed stent grafts. Unfortunately, most stent grafts are designed for treating aortic aneurysmal disease instead of traumatic injury. Further refinements in stent graft technology depend on a thorough anatomic understanding of the transection injury process. METHODS: All patients with computed tomography (CT) evidence of blunt aortic injury (BAI) between 2006 and 2012 at a Level 1 trauma center were queried. Their initial CT scans were imported into the Intuition (Terarecon, Inc.) viewing program, and off-line centerline reconstruction was performed. Standard demographic data were collected in addition to anatomic characteristics, including aortic diameters and the relationship of the injury to the arch vessels. RESULTS: Thirty-five patients were identified. Three patients were injured proximal to the left subclavian artery. The average length from the left subclavian artery to the proximal site of injury was 16.2 mm (range 2-31 mm). Most patients had >15 mm of landing zone beyond the left subclavian artery. The range of proximal diameters ranged from 17 to 32 mm, with an average aortic diameter of 23.9 mm. The average length of injured aortic segment was 27 mm. CONCLUSIONS: In this contemporary series from a large trauma center, 91% of patients are anatomically able to be treated with a stent graft that does not require coverage of the left common carotid artery. Most patients have an aortic diameter that falls between 21 and 26 mm in diameter, as well as a short segment of injured artery. Centers interested in emergently treating aortic transections are able to do so while maintaining a limited stock of stent grafts that can be used to treat the majority of the population.

The effect of recent chemotherapy in aorto-iliac aneurysm repair.

The aim of the study was to investigate the effect of recent chemotherapy (Chx) on outcome of aorto-iliac aneurysm (AAA) repair. The 2005-2010 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify vascular patients undergoing AAA repair within 30 days after Chx. Seventy-one patients underwent AAA repair within 30 days of receiving Chx, group A (71 ± 8.4 years, 77.5% males) and 20,024 patients underwent AAA repair without prior Chx, group B (73 ± 9 years, 79.2% males). The two groups did not significantly differ with respect to open or endovascular repair (open repair A: 32%, B: 35%, P = 0.66). However, patients in group A presented more often as emergent cases (A: 27%, B: 12%, P = 0.001). Multivariable regression analysis for emergent cases after adjustment for relevant confounders also demonstrated that patients with recent Chx present more often as emergency (P = 0.001, odds ratio [OR]: 2.4). Thirty-day non-surgical complications were more common in group A (A: 25%, B: 16.5%, P = 0.046) while surgical complications were equivalent (A: 15.5%, B: 12.3%, P = 0.414). Risk of death was significantly higher in group A in univariate analysis (A: 13%, B: 5%, P = 0.005, OR: 2.6). Patients who receive Chx within 30 days prior to AAA repair present more frequently as emergencies leading to higher mortality. The reason for this cannot be sufficiently explained by the current database but patient selection for elective repair or the effect of Chx on the natural course of AAA may play a role.

Endovascular vs open repair of renal artery aneurysms: outcomes of repair and long-term renal function.

BACKGROUND: Endovascular treatment (ER) of renal artery aneurysms (RAA) has been widely used recently due to its assumed lower morbidity and mortality compared with open surgery (OS). The purpose of this study was to investigate the outcomes of OS and ER, and compare long-term renal function. STUDY DESIGN: Data from 2000 to 2012 were retrospectively collected to identify patients who were treated for RAA in a single institution. Morbidity, mortality, freedom from reinterventions, and renal function were compared between OS and ER for RAA. RESULTS: Forty-four RAA repairs were identified in 40 patients (28 women, mean age ± SD 54 ± 13 years). Twenty RAA were repaired with OS (45%) and 24 RAA (55%) with ER. Mean aneurysm sizes were 2.5 ± 1.5 cm (OS) and 2.2 ± 2.2 cm (ER; p = 0.66). Endovascular repair included coil embolization with or without stent placement in 19 patients (79%) and stent grafts in 4 (17%). Open surgery included excision or aneurysmorrhaphy of the aneurysm in 11 kidneys (55%), graft interposition or bypass in 4 (20%), and 4 nephrectomies (20%). There was 1 technical failure in each group. Comorbidities were similar between the 2 groups (American Society of Anesthesiologists III-IV: OS, 40%; ER, 58%; p = 0.44). Endovascular repair and OR had equivalent perioperative morbidity (any complication OS, 15%, ER, 17%, p = 1.0) and no mortality (OS, 0%, ER, 0%). Endovascular repair was associated with shorter hospitalization (OS, 6.3 ± 2.5; ER, 2 ± 3.4 days, p < 0.001). Mean follow-ups were 21 ± 32 months (OS) and 27 ± 36 months (ER). A 30% reduction in glomerular filtration rate occurred in 12.5% of OS patients and 9.1% of ER patients (p = 1.00). Freedom from reintervention at 12 and 24 months were OS, 82%/82% and ER, 82%/74%, respectively (log-rank-test = 0.23). CONCLUSIONS: Endovascular repair of RAA is as safe and effective as open repair in selected patients with appropriate anatomy. There was no difference in decline in renal function between OS and ER.

Persistent left sciatic artery eliminated need for revascularization in a 13-year-old with pseudoaneurysm of the superficial femoral artery.

Persistent sciatic artery (PSA) is an anatomical variation which is rare and most frequently diagnosed secondary to its clinical complications. The sciatic artery walls have a tendency to aneurysmal degeneration and may evolve to thrombosis or thromboembolism. This article reports the case of a 13-year-old male patient with left superficial femoral artery pseudoaneurysm after gunshot wound and complete PSA with in-line flow to the popliteal artery as incidental finding. The patient underwent coil embolization of the pseudoaneurysm with the sciatic artery left intact. The technical aspects are discussed and the literature on diagnosis and therapeutic approach of this anatomical variation is reviewed.

Late Gore Excluder endoprosthesis fabric tear leading to abdominal aortic aneurysm rupture 5 years after initial implant.

Endoprosthesis fabric tear leading to abdominal aortic aneurysm rupture is a rare event. In this report, we describe a patient who presented with an abdominal aortic aneurysm rupture after a tear in the fabric of the Gore Excluder endoprosthesis (W. L. Gore and Associationes, Flagstaff, Ariz) 5 years after implantation. The reason for the fabric tear was unknown. The complication was successfully treated by relining the endograft with an aortic cuff and two iliac limbs. The patient experienced an uneventful recovery after the intervention.

Characterization of resident surgeon participation during carotid endarterectomy and impact on perioperative outcomes.

INTRODUCTION: The impact of resident surgeon participation during vascular procedures on postoperative outcomes is incompletely understood. We characterized resident physician participation during carotid endarterectomy (CEA) procedures within the 2005-2009 American College of Surgeons National Surgical Quality Improvement Participant Use Datafile and evaluated associations with procedural characteristics and perioperative adverse events. METHODS: CEAs were identified using primary current procedural terminology codes; those performed simultaneously with other major procedures or unknown resident participation status were excluded. Group-wise comparisons based on resident participation status were performed using χ(2) or Fisher's exact test for categorical variables and t tests or nonparametric methods for continuous variables. Associations with perioperative adverse events (major = stroke, death, myocardial infarction, or cardiac arrest; minor = peripheral nerve injury, bleeding requiring transfusion, surgical site infection, or wound disruption) were assessed using multivariable logistic regression models adjusting for other known risk factors. RESULTS: A total of 25,280 CEA procedures were analyzed, of which residents participated in 13,705 (54.2%), while residents were absent in 11,575 (45.8%). Among CEAs with resident physician participation, resident level was categorized as junior (postgraduate year [PGY] 1-2) in 21.9%, senior (PGY 3-5) in 52.7%, and fellow (PGY ≥6) in 25.3%. Major adverse event rates with and without resident participation were 1.9% versus 2.1%, and minor adverse event rates with and without resident participation were 0.9% versus 1.0%, respectively. In multivariable models, resident physician participation was not associated with perioperative risk for major adverse events (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.75-1.08) or minor adverse events (OR, 0.93; 95% CI, 0.72-1.21). CONCLUSIONS: Resident surgeon participation during CEA is not associated with risk of adverse perioperative events.

Endovascular management of a ruptured thoracoabdominal aneurysm-damage control with superior mesenteric artery snorkel and thoracic stent-graft exclusion.

We report a case of a large ruptured thoracoabdominal aortic aneurysm, which was stabilized with endovascular aortic exclusion and snorkel bypass of the superior mesenteric artery (SMA). An 80-year-old African American woman with multiple medical comorbidities and previous open infrarenal abdominal aortic aneurysm repair presented with a ruptured 10.7 × 7.3 cm thoracoabdominal aortic aneurysm involving the origins of the renal and mesenteric vessels. The patient underwent emergent endovascular aortic repair with placement of a covered stent into the SMA coursing parallel to the aortic endograft. This technique was initially successful in clinically stabilizing the patient; however; 3 weeks after the initial procedure, she presented with recurrent rupture necessitating proximal extension of her snorkeled SMA bypass and aortic endograft into the mid-descending thoracic aorta. The patient stabilized and was successfully discharged home.

Simultaneous arterial and venous ultrasound-assisted thrombolysis for phlegmasia cerulea dolens.

Phlegmasia cerulea dolens is a rare condition in which an extensive deep venous thrombus can partially or completely occlude venous outflow from the affected extremity. Clinical presentation is typically characterized by extremity edema, cyanosis, and pain. This condition is associated with a high rate of extremity amputation and mortality. Although numerous therapies have been described, there is no generalized treatment consensus and less invasive forms of therapy continue to evolve. We report a case of phlegmasia cerulea dolens in a patient who presented with concomitant arterial and venous thrombosis of the affected extremity. The patient's condition was successfully treated using combined ultrasound-assisted intra-arterial and intravenous catheter-directed thrombolysis.

The incidence of microemboli to the brain is less with endarterectomy than with percutaneous revascularization with distal filters or flow reversal.

BACKGROUND: Current data suggest microembolization to the brain may result in long-term cognitive dysfunction despite the absence of immediate clinically obvious cerebrovascular events. We reviewed a series of patients treated electively with carotid endarterectomy (CEA), carotid artery stenting (CAS) with distal filters, and carotid stenting with flow reversal (FRS) monitored continuously with transcranial Doppler scan (TCD) during the procedure to detect microembolization rates. METHODS: TCD insonation of the M1 segment of the middle cerebral artery was conducted during 42 procedures (15 CEA, 20 CAS, and 7 FRS) in 41 patients seen at an academic center. One patient had staged bilateral CEA. Ipsilateral microembolic signals (MESs) were divided into three phases: preprotection phase (until internal carotid artery [ICA] cross-shunted or clamped if no shunt was used, filter deployed, or flow reversal established), protection phase (until clamp/shunt was removed, filter removed, or antegrade flow re-established), and postprotection phase (after clamp/shunt was removed, filter removed, or antegrade flow re-established). Descriptive statistics are reported as mean ± SE for continuous variables and N (%) for categorical variables. Differences in ipsilateral emboli counts based on cerebral protection strategy were assessed using nonparametric methods. RESULTS: TCD insonation and procedural success were obtained in 33 procedures (79%; 14 CEA, 14 CAS, and 5 FRS). Highest ipsilateral MESs were observed for CAS (319.3 ± 110.3), followed by FRS (184.2 ± 110.5), and CEA (15.3 ± 22.0). Pairwise comparisons revealed significantly higher ipsilateral MESs with both FRS and CAS when compared to CEA (P = .007 for FRS and P < .001 for CAS vs CEA, respectively), whereas the difference in MESs between FRS and CAS was not significant (P = .053). Periods of maximum embolization were postprotection phase for CEA, protection phase for CAS, and preprotection phase for FRS. Preprotection MESs were frequently observed during both CAS and FRS (20.4% and 63.3% of total MESs across all phases, respectively), and the primary difference between these two methods seemed to be related to lower MESs during the protection phase with FRS. CONCLUSION: CEA is associated with lower rates of microembolization compared with carotid stenting. Flow reversal may represent a procedural modification with potential to reduce microembolization during carotid stenting; further investigation is warranted to determine the relationship between cerebral protection strategies and outcomes associated with carotid stenting.

Persistent beneficial effect of postconditioning against infarct size: role of mitochondrial K(ATP) channels during reperfusion.

UNLABELLED: This study tested the hypothesis that inhibition of myocardial injury and modulation of mitochondrial dysfunction by postconditioning (Postcon) after 24 h of reperfusion is associated with activation of K(ATP) channels. Thirty dogs undergoing 60 min of ischemia and 24 h of reperfusion (R) were randomly divided into four groups: CONTROL: no intervention at R; Postcon: three cycles of 30 s R alternating with 30 s re-occlusion were applied at R; 5-hydroxydecanoate (5-HD): the mitochondrial K(ATP) channel blocker was infused 5 min before Postcon; HMR1098: the sarcolemmal K(ATP) channel blocker was administered 5 min before Postcon. After 24 h of R, infarct size was smaller in Postcon relative to CONTROL (27 +/- 4%* Vs. 39 +/- 2% of area at risk), consistent with a reduction in CK activity (66 +/- 7* Vs. 105 +/- 7 IU/g). The infarct-sparing effect of Postcon was blocked by 5-HD (48 +/- 5%(dagger)), but was not altered by HMR1098 (29 +/- 3%*), consistent with the change in CK activity (102 +/- 8(dagger) in 5-HD and 71 +/- 6* IU/g in HMR1098). In H9c2 cells exposed to 8 h hypoxia and 3 h of reoxygenation, Postcon up-regulated expression of mito-K(ATP) channel Kir6.1 protein, maintained mitochondrial membrane potential and inhibited mitochondrial permeability transition pore (mPTP) opening evidenced by preserved fluorescent TMRE and calcein staining. The protective effects were blocked by 5-HD, but not by HMR1098. These data suggest that in a clinically relevant model of ischemia-reperfusion (1) Postcon reduces infarct size and decreases CK activity after prolonged reperfusion; (2) protection by Postcon is achieved by opening mitochondrial K(ATP) channels and inhibiting mPTP opening. *P < 0.05 Vs. CONTROL; P < 0.05 Vs. Postcon.

Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation.

Opioids introduced at reperfusion (R) following ischemia (I) reduce infarct size much like postconditioning, suggesting the hypothesis that postconditioning increases cardiac opioids and activates local opioid receptors. Anesthetized male rats subjected to 30 min regional I and 3 h R were postconditioned with three cycles of 10 s R and 10 s reocclusion at onset of R. Naloxone (NL), its peripherally restricted analog naloxone methiodide, delta-opioid receptor (DOR) antagonist naltrindole (NTI), kappa-opioid receptor antagonist norbinaltorphimine (NorBNI), and mu-opioid receptor (MOR) antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were administered intravenously 5 min before R. The area at risk (AAR) was comparable among groups, and postconditioning reduced infarct size from 57 +/- 2 to 42 +/- 2% (P < 0.05). None of the antagonists alone altered infarct size. All antagonists abrogated postconditioning protection at higher doses. However, blockade of infarct sparing by postconditioning was lost, since tested doses of NL, NTI, NorBNI, and CTAP were lowered. The efficacy of NorBNI declined first at 3.4 micromol/kg, followed sequentially by NTI (1.1), NL (0.37), and CTAP (0.09), suggesting likely MOR and perhaps DOR participation. Representative small, intermediate, and large enkephalins in the AAR were quantified (fmol/mg protein; mean +/- SE). I/R reduced proenkephalin (58 +/- 9 vs. 33 +/- 4; P < 0.05) and sum total of measured enkephalins, including proenkephalin, peptide B, methionine-enkephalin, and methionine-enkephalin-arginine-phenylalanine (139 +/- 17 vs. 104 +/- 7; P < 0.05) compared with shams. Postconditioning increased total enkephalins (89 +/- 8 vs. 135 +/- 5; P < 0.05) largely by increasing proenkephalin (33 +/- 4 vs. 96 +/- 7; P < 0.05). Thus the infarct-sparing effect of postconditioning appeared to involve endogenously activated MORs and possibly DORs, and preservation of enkephalin precursor synthesis in the AAR.

PAR-2 activation at the time of reperfusion salvages myocardium via an ERK1/2 pathway in in vivo rat hearts.

Protease-activated receptor-2 (PAR-2) may have proinflammatory effects in some tissues and protective effects in other tissues. The role of PAR-2 in in vivo myocardial ischemia-reperfusion has not yet been determined. This study tested the hypothesis that PAR-2 activation with the PAR-2 agonist peptide SLIGRL (PAR-2 AP) reduces myocardial infarct size when given at reperfusion in vivo, and this cardioprotection involves the ERK1/2 pathway. Anesthetized rats were randomly assigned to the following groups with 30 min of regional ischemia and 3 h reperfusion: 1) control with saline; 2) vehicle (DMSO); 3) PAR-2 AP, 1 mg/kg given intravenously 5 min before reperfusion; 4) scrambled peptide (SP), 1 mg/kg; 5) the ERK1/2 inhibitor PD-98059 (PD), 0.3 mg/kg given 10 min before reperfusion; 6) the phosphatidylinositol 3-kinase inhibitor LY-294002 (LY), 0.3 mg/kg given 10 min before reperfusion; 7) PD + PAR-2 AP, 0.3 mg/kg PD given 5 min before PAR-2 AP; 8) LY + PAR-2 AP, 0.3 mg/kg LY given 5 min before PAR-2 AP; 9) chelerythrine (Chel) alone, 5 mg/kg given 10 min before reperfusion; and 10) Chel + PAR-2 AP, Chel was given 5 min before PAR-2 AP (10 min before reperfusion). Activation of ERK1/2, ERK5, Akt, and the downstream targets of ERK1/2 [P90 RSK and bcl-xl/bcl-2-associated death promoter (BAD)] was determined by Western blot analysis in separate experiments. PAR-2 AP significantly reduced infarct size compared with control (36 +/- 2% vs. 53 +/- 1%, P < 0.05), and SP had no effect on infarct size (53 +/- 3%). PAR-2 AP significantly increased phosphorylation of ERK1/2, p90RSK, and BAD but not Akt or ERK5. Accordingly, the infarct-size sparing effect of PAR-2 AP was abolished by PD (PAR-2 AP, 36 +/- 2% vs. PD + PAR-2 AP, 50 +/- 1%; P < 0.05) and by Chel (Chel + PAR-2 AP, 58 +/- 2%) but not by LY (PAR-2 AP, 36 +/- 2% vs. LY + PAR-2 AP, 38 +/- 3%; P > 0.05). Therefore, PAR-2 activation is cardioprotective in the in vivo rat heart ischemia-reperfusion model, and this protection involves the ERK1/2 pathway and PKC.

Inflammation, proinflammatory mediators and myocardial ischemia-reperfusion Injury.

Ischemic myocardium must be reperfused to terminate the ischemic event; otherwise the entire myocardium involved in the area at risk will not survive. However, there is a cost to reperfusion that may offset the intended clinical benefits of minimizing infarct size, postischemic endothelial and microvascular damage, blood flow defects, and contractile dysfunction. There are many contributors to this reperfusion injury. Targeting only one factor in the complex web of reperfusion injury is not effective because the untargeted mechanisms induce injury. An integrated strategy of reducing reperfusion injury in the catheterization laboratory involves controlling both the conditions and the composition of the reperfusate. Mechanical interventions such as gradually restoring blood flow or applying postconditioning may be used independently in or conjunction with various cardioprotective pharmaceuticals in an integrated strategy of reperfusion therapeutics to reduce postischemic injury.

Long-term inhibition of myocardial infarction by postconditioning during reperfusion.

Cardioprotection with postconditioning has been well demonstrated after a short period of reperfusion. This study tested the hypothesis that postconditioning reduces infarct size, vascular dysfunction, and neutrophil accumulation after a long-term reperfusion. Canines undergoing 60 min left anterior descending artery (LAD) occlusion were divided into two control groups of either 3 h or 24 h of full reperfusion and two postconditioning groups with three 30 s cycles of reperfusion and re-occlusion applied at the onset of either 3 h or 24 h of reperfusion. Size of the area at risk (AAR) and collateral blood flow during ischemia were similar among groups. In controls, infarct size as percentage of the AAR (30 +/- 3 vs. 39 +/- 2* %) by TTC staining, superoxide anion generation from the post-ischemic coronary arteries by lucigenin-enhanced chemiluminescence [(89 +/- 5 vs. 236 +/- 27* relative light units (RLU/mg)], and neutrophil (PMN) accumulation by immunohistochemical staining in the AAR (52 +/- 11 vs. 84 +/- 14* cells/mm(2) myocardium) significantly increased between 3 and 24 h of reperfusion. Postconditioning reduced infarct size (15 +/- 4 and 27 +/- 3.6 %), superoxide anion generation (24 +/- 4 and 43 +/- 11 RLU/mg), and PMN accumulation (19 +/- 6 and 45 +/- 8 cells/mm(2) myocardium) in the 3 and 24 h reperfusion groups relative to time-matched controls. These data suggest that myocardial injury increases with duration of reperfusion; reduction in infarct size and attenuation in inflammatory responses with postconditioning persist after a prolonged reperfusion. * p < 0.05 24 vs. 3 h control; p < 0.05 postconditioning vs. time-matched control.